Leflunomide in Treating Patients With High-Risk Smoldering Multiple Myeloma

NCT03952832 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 18458NCI-2019-00247
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well leflunomide works in treating patients with high-risk smoldering multiple myeloma. Leflunomide may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Smoldering Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

• Progression to multiple myeloma

  Progression to multiple myeloma in the absence of increased calcium level, renal dysfunction, anemia, and destructive bone lesions (CRAB) features, orto symptomatic multiple myeloma that requires therapy will be assessed.

  Up to 2 years

• Overall survival

  Overall survival will be estimated using the product-limit method of Kaplan and Meier.

  Up to 2 years

Secondary Outcomes (4)

• Overall response rate (ORR)

  Up to 2 years

• Incidence of adverse events (AEs)

  Up to 30 days post treatment

• Freedom from progression

  Up to 2 years

• Change in quality of life

  Baseline up to 2 years

Study Arms (1)

Treatment (leflunomide)

EXPERIMENTAL

Patients receive leflunomide PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Leflunomide; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Leflunomide DRUG

Given PO

Also known as: Arava, SU101

Treatment (leflunomide)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (leflunomide)

Questionnaire Administration OTHER

Ancillary studies

Treatment (leflunomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must have the ability to understand and the willingness to sign a written informed consent
• Patients must have a life expectancy of \> 3 months
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Patients must have a diagnosis of high risk smoldering multiple myeloma, as defined below:
• The presence of \>= 2 of the following risk factors:
• Bone marrow plasma cell percentage (BMPC%) \> 20%
• Serum M-protein \> 2 g/dL
• Free light chain ratio (FLCr) \> 20
• At least 2 weeks from prior therapy to time of start of treatment; prior therapy includes steroids (except prednisone or equivalent - up to 10 mg per day is allowed)
• Platelet count \>= 50,000/uL. Platelet transfusions are not allowed within 14 days of platelet assessment
• Absolute neutrophil count (ANC) \>= 1000/mm\^3
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.0 x upper limits of normal (ULN)
• Total bilirubin \< 1.5 x ULN
• Calculated creatinine clearance (CrCl) \>= 30 mL/min per 24-hour urine collection or the Cockcroft-Gault formula
• Negative serum or urine beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential\* only), to be performed locally within the screening period

You may not qualify if:

• Prior treatment with leflunomide
• Prior treatment for smoldering multiple myeloma
• Current or planned use of other investigational agents, or concurrent biological, chemotherapy, or radiation therapy during the study treatment period; current or planned growth factor or transfusion support until after initiation of treatment; if growth factor or transfusion support is provided between screening and start of treatment, the participant will no longer be eligible
• Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
• Hypercalcemia: serum calcium \> 0.25 mmol/L (\> 1 mg/dL) higher than the upper limit of normal or \> 2.75 mmol/L (\> 11 mg/dL)
• Renal insufficiency: creatinine clearance \< 40 mL per min or serum creatinine \> 177 umol/L (\> 2 mg/dL)
• Anemia: hemoglobin value of \> 20 g/L below the lower limit of normal, or a hemoglobin value \< 10 g/dL
• Bone lesions: one or more osteolytic lesions on skeletal radiography, computer tomography (CT), or positron emission tomography (PET)-CT
• Any one or more of the following biomarkers of malignancy:
• Clonal bone marrow plasma cell percentage \>= 60%
• Involved: uninvolved serum free light chain ratio \>= 100 (Involved free light chain must be \>= 100 mg/L) \>= 1 focal lesions on magnetic resonance imaging (MRI) studies (\>=5 mm in size each)
• Participants with increased calcium level, renal dysfunction, anemia, and destructive bone lesions (CRAB) criteria that are attributable to conditions other than the disease under study may be eligible
• Prior diagnosis of rheumatoid arthritis
• Prior allogeneic transplant
• Acute active infection requiring systemic therapy within 2 weeks prior to enrollment

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Smoldering Multiple Myeloma

Interventions

Leflunomide

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michael Rosenzweig

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2019
• First Posted: May 16, 2019
• Study Start: December 11, 2019
• Primary Completion: June 11, 2021
• Study Completion: June 11, 2021
• Last Updated: November 14, 2019

Record last verified: 2019-11

Locations

US (1)